Methods of making polynucleotides are known. One method for large-scale de novo DNA synthesis includes use of automated instruments employing solid phase phosphoramidite chemistry first developed by Beaucage and Caruthers. This chemistry is widely practiced in a 3-4 step process on solid support, involving iterative pH-mediated deprotection and coupling in organic solvents. Typically, this automated process synthesizes up to 384 oligos simultaneously at scales up to 100 nmol. Length limitations and error rates of this process exist due to exponentially decaying full length oligo fractions due to compounding sub-unity stepwise yields and destructive side reactions, such as acidic depurination.